MOUSE PHENOTYPING, PHYSIOLOGY, AND METABOLISM CORE: Director - R. Ahima Our understanding of the pathogenesis of diabetes has benefited from the use of gene targeting methodology in mice to elucidate molecular mechanisms. However, such efforts are often hampered by an absence of a clear metabolic phenotype. Failure to identify a phenotype may be due to lack of expertise and/or facilities for evaluating metabolic changes in mice. The Mouse Phenotyping, Physiology and Metabolism Core provides investigators of the Penn Diabetes and Endocrinology Research Center (DERC) with state-of-the-art, timely and cost-effective diagnostic studies in mice. The core offers consultation and experimental design, monitoring of feeding, energy expenditure and locomotor activity using the Comprehensive Laboratory Animal Monitoring System (CLAMS), treadmill exercise using the Oxymax system, and measurement of body composition using dual emission x-ray absorptiometry (DEXA) and carcass chemistry. Glucose homeostasis is assessed by oral or intraperitoneal (i.p.) glucose administration, and whole body insulin sensitivity by i.p. insulin injection. Insulin clamp and radioactive tracers are used to assess glucose fluxes and tissue specific glucose uptake. Studies in the core are performed by two research specialists under the direction of Rex Ahima. Future plans for the core include the use magnetic resonance (MRI) for measurement of water, lean and fat content, assessment of in vivo lipid kinetics, and employment of an additional technician to expedite services. The Mouse Phenotyping, Physiology and Metabolism Core will maintain a databank of metabolic and hormonal parameters in mouse models of diabetes and obesity, and coordinate its activities with other core laboratories, i.e. Islet Cell Biology (Franz Matschinsky), Radioimmunoassay/Biomarkers (Bryan Wolf;Muredach Reilly), Transgenic and Chimeric Mouse (Nancy Cooke), and Genomics and Gene Targeting Cores (Klaus Kaestner). These efforts will result in optimum data acquisition and metabolic phenotyping of mice, and facilitate the translation of ideas from the bench to mice, and ultimately to humans.